Monocarboxylate transporters facilitate succinate uptake into brown adipocytes.

Uptake of circulating succinate by brown adipose tissue (BAT) and beige fat elevates whole-body energy expenditure, counteracts obesity and antagonizes systemic tissue inflammation in mice. The plasma membrane transporters that facilitate succinate uptake in these adipocytes remain undefined. Here we elucidate a mechanism underlying succinate import into BAT via monocarboxylate transporters (MCTs).

Peripheral Administration of Norepinephrine: A Prospective Observational Study.

Background: Historically, norepinephrine has been administered through a central venous catheter (CVC) because of concerns about the risk of ischemic tissue injury if extravasation from a peripheral IV catheter (PIVC) occurs. Recently, several reports have suggested that peripheral administration of norepinephrine may be safe.

Research Question: Can a protocol for peripheral norepinephrine administration safely reduce the number of days a CVC is in use and frequency of CVC placement?

Study Design And Methods: This was a prospective observational cohort study conducted in the medical ICU at a quaternary care academic medical center.

Monocarboxylate transporters facilitate succinate uptake into brown adipocytes.

Uptake of circulating succinate by brown adipose tissue (BAT) and beige fat elevates whole body energy expenditure, counteracts obesity, and antagonizes systemic tissue inflammation in mice. The plasma membrane transporters that facilitate succinate uptake in these adipocytes remain undefined. Here we elucidate a mechanism underlying succinate import into BAT via monocarboxylate transporters (MCTs).

Association of Arterial pH With Hemodynamic Response to Vasopressin in Patients With Septic Shock: An Observational Cohort Study.

Objectives: Vasopressin is reported to retain vasoconstrictive activity in the setting of acidemia, but preclinical models are inconsistent and studies have not evaluated the clinical effectiveness of vasopressin based on arterial pH. This study sought to determine the association between arterial pH and blood pressure after vasopressin initiation in septic shock.

Design: This retrospective, multicenter, observational cohort study evaluated the association of arterial pH at the time of vasopressin initiation with hemodynamic response to vasopressin and change in catecholamine dose after vasopressin initiation.

Retrospective evaluation of a delirium order set utilizing nonpharmacologic and pharmacologic interventions for the treatment of delirium in medical intensive care unit patients.

Purpose: To describe the use of a medical intensive care unit (MICU) delirium order set pilot and its associated impact on utilization of nonpharmacologic and pharmacologic interventions, pharmacologic continuation at transitions of care, and resolution of ICU delirium.

Methods: This was a retrospective cohort analysis of MICU patients who received delirium management using an order set pilot compared to standard care. Patients 18 years of age or older admitted to the MICU between May 2019 and January 2020 who received an antipsychotic or valproic acid for the treatment of delirium were included.

Glucose metabolism and pyruvate carboxylase enhance glutathione synthesis and restrict oxidative stress in pancreatic islets.

Glucose metabolism modulates the islet β cell responses to diabetogenic stress, including inflammation. Here, we probed the metabolic mechanisms that underlie the protective effect of glucose in inflammation by interrogating the metabolite profiles of primary islets from human donors and identified de novo glutathione synthesis as a prominent glucose-driven pro-survival pathway. We find that pyruvate carboxylase is required for glutathione synthesis in islets and promotes their antioxidant capacity to counter inflammation and nitrosative stress.

Association of Catecholamine Dose, Lactate, and Shock Duration at Vasopressin Initiation With Mortality in Patients With Septic Shock.

Objectives: To determine the association of catecholamine dose, lactate concentration, and timing from shock onset at vasopressin initiation with in-hospital mortality.

Design: Retrospective, observational study using segmented and multivariable logistic regression to evaluate the associations of catecholamine dose, lactate concentration, and timing from shock onset at vasopressin initiation with in-hospital mortality.

Setting: Multiple hospitals within the Cleveland Clinic Health System.

Reinfection Rates Among Patients Who Previously Tested Positive for Coronavirus Disease 2019: A Retrospective Cohort Study.

Background: Protection afforded from prior disease among patients with coronavirus disease 2019 (COVID-19) infection is unknown. If infection provides substantial long-lasting immunity, it may be appropriate to reconsider vaccination distribution.

Methods: This retrospective cohort study of 1 health system included 150 325 patients tested for COVID-19 infection via polymerase chain reaction from 12 March 2020 to 30 August 2020.

Home testing for COVID-19: Benefits and limitations.

The home test kits for detecting SARS-CoV-2 infection with Food and Drug Administration emergency use authorization primarily use either isothermal nucleic acid amplification or antigen detection, and each test has advantages and limitations in terms of sensitivity and specificity, cost, results reporting, and results turnaround time. In clinical studies, these tests provide accurate positive results in symptomatic individuals, although negative results are less accurate. There are also accuracy concerns for positive results in asymptomatic individuals.

Choosing Wisely For Critical Care: The Next Five.

Objectives: To formulate new "Choosing Wisely" for Critical Care recommendations that identify best practices to avoid waste and promote value while providing critical care.

Data Sources: Semistructured narrative literature review and quantitative survey assessments.

Study Selection: English language publications that examined critical care practices in relation to reducing cost or waste.

Effect of Phenylephrine Push Before Continuous Infusion Norepinephrine in Patients With Septic Shock.

Background: IV pushes of phenylephrine may be used for patients with septic shock with the intent of rapidly achieving mean arterial pressure (MAP) goals. However, the clinical effectiveness and safety of this approach are unclear.

Research Question: In patients with septic shock, is administration of a phenylephrine push before norepinephrine initiation associated with a higher incidence of hemodynamic stability?

Methods: This retrospective, multicenter cohort study included adult patients with septic shock initiated on norepinephrine.

Hemodynamic Response to Vasopressin Dosage of 0.03 Units/Min vs. 0.04 Units/Min in Patients With Septic Shock.

Background: Arginine vasopressin (AVP) is suggested as an adjunct to norepinephrine in patients with septic shock. Guidelines recommend an AVP dosage up to 0.03 units/min, but 0.

Effectiveness and Safety of Twice Daily Versus Thrice Daily Subcutaneous Unfractionated Heparin for Venous Thromboembolism Prophylaxis at a Tertiary Medical Center.

Background: The direct comparison of twice daily (BID) and thrice daily (TID) dosing of subcutaneous low dose unfractionated heparin (LDUH) for venous thromboembolism (VTE) prophylaxis in a mixed inpatient population is not well-studied.

Objective: This study evaluated the effectiveness and safety of BID compared to TID dosing of LDUH for prevention of VTE.

Methods: Retrospective, single-center analysis of patients who received LDUH for VTE prophylaxis between July and September 2015.

pH-Gated Succinate Secretion Regulates Muscle Remodeling in Response to Exercise.

In response to skeletal muscle contraction during exercise, paracrine factors coordinate tissue remodeling, which underlies this healthy adaptation. Here we describe a pH-sensing metabolite signal that initiates muscle remodeling upon exercise. In mice and humans, exercising skeletal muscle releases the mitochondrial metabolite succinate into the local interstitium and circulation.

Abrupt Discontinuation Versus Down-Titration of Vasopressin in Patients Recovering from Septic Shock.

Purpose: To compare patient outcomes based on management of arginine vasopressin (AVP) during the recovery phase of septic shock (abrupt vs. tapering discontinuation).

Patients And Methods: Multicenter, retrospective cohort study of patients receiving AVP with concomitant norepinephrine for septic shock.

Design, creation and in vitro testing of a reduced immunogenicity humanized anti-CD25 monoclonal antibody that retains functional activity.

Humanized and fully human sequence-derived therapeutic antibodies retain the capacity to induce anti-drug antibodies. Daclizumab (humanized version of the murine anti-Tac antibody; E.HAT) was selected for a proof of concept application of engineering approaches to reduce potential immunogenicity due to its demonstrated immunogenicity in the clinic.

Interhospital transport of patients with COVID-19: Cleveland Clinic approach.

Hospital-to-hospital transportation of patients in the COVID-19 era presents unique challenges to ensuring the safety of both patients and health care providers. Crucial factors to address include having adequate supplies of protective equipment and ensuring their appropriate use, defining patient care procedures during transport, and decontamination post-transport. Transport vehicles need to have adequate physical space, an isolated driver compartment, NS HEPA filtration of air.